Quantum dots and nanoparticles for photodynamic and radiation therapies of cancer

Abstract

Semiconductor quantum dots and nanoparticles composed of metals, lipids or polymers have emerged with promising applications for early detection and therapy of cancer. Quantum dots with unique optical properties are commonly composed of cadmium contained semiconductors. Cadmium is potentially hazardous, and toxicity of such quantum dots to living cells, and humans, is not yet systematically investigated. Therefore, search for less toxic materials with similar targeting and optical properties is of further interest. Whereas, the investigation of luminescence nanoparticles as light sources for cancer therapy is very interesting. Despite advances in neurosurgery and radiotherapy the prognosis for patients with malignant gliomas has changed little for the last decades. Cancer treatment requires high accuracy in delivering ionizing radiation to reduce toxicity to surrounding tissues. Recently some research has been focused in developing photosensitizing quantum dots for production of radicals upon absorption of visible light. In spite of the fact that visible light is safe, this approach is suitable to treat only superficial tumours. Ionizing radiation (X-rays and gamma rays) penetrate much deeper thus offering a big advantage in treating patients with tumours in internal organs. Such concept of using quantum dots and nanoparticles to yield electrons and radicals in photodynamic and radiation therapies as well their combination is reviewed in this article.

Fig. 1

Schematic presentation of the most likely events occurring when a photon hits a quantum dot. Situation for a low-energy photon (ultraviolet, visible light, near infrared radiation): I) Charge transfer, where QD is a donor and A is an acceptor molecule, ΔE_g is the energy gap of the quantum dot, e⁻ and h⁺ is an electron-hole pair generated by the absorption of the photon, II) Photosensitization, where the quantum dot is promoted from its ground state (a) to a higher energy excited state (b) and then to a “trap” state (c), from which by TET triplet ground-state oxygen (³O₂) is promoted into a highly reactive singlet oxygen (¹O₂). Vibrational levels are depicted for illustrative purpose. Dashed arrows show non-radiative transitions. Situation for a high-energy photon (X-rays and gamma rays): III) Ejection of a high speed electron from an atom constituting the quantum dot due to the photon energy transfer to the electron (photoelectric ionization effect) or Compton scattering, where the incident photon is scattered continuing its voyage with lower energy until next event, IV) Photon annihilation on a nucleus of an atom and generation of an electron-positron pair. The positron will annihilate with a free electron releasing two 0.51 MeV photons, which will further lose their energy through photoelectric effect or Compton scattering. Electrons generated in the events III and IV will induce secondary high speed electrons as well as Auger electrons. Such electrons that succeed to escape into environment will be captured by an acceptor (water, biomolecule, oxygen, nitrogen oxides) in the vicinity of the quantum dot and induce biomolecular radicals, superoxide, hydroxyl radical, peroxynitrite anion or nitric oxide radical.

Fig. 2

Simplified diagram illustrating energy levels of a quantum dot compared to its semiconductor material in a bulk crystal. Electrons and holes in the quantum dot and the semiconductor crystal obey Pauli’s exclusion principle when filling the energy states and their positions are shown schematically only. Adapted from Ref. [11].

Fig. 3

Fluorescence microscopy detection of PPEI-EI-functionalized carbon dots in MCF-7 cells with one-photon (458 nm) and two-photon (800 nm) excitations. Shown in the insets are signals likely associated with single carbon dots.

Fig. 4

Enhancement of fluorescence of quantum dots (8 nM QD655-carboxyl terminated) endocytosed in Du145 cells (5×10⁵ cells/ml). A) Fluorescence microscopy photograph (objective 40×) taken within 0–1 min of observation after around 24 h incubation. Nuclei are stained with Hoechst 33342. B) The same spot on the culture dish photographed under the same conditions after 5 min irradiation with the microscope excitation light (395–440 nm). Red fluorescence appears while the Hoechst dye is photobleached during irradiation. C) Fluorescence photograph taken at lower magnification (10×) highlights the red fluorescent spot caused by the irradiation using the 40× objective. The scale bars are 100 μm.

Fig. 5

Schematic presentation of the nanoparticle-based X-ray-induced PDT. Under ionizing radiation a nanoparticle starts to scintillate transferring its energy into a conjugated porphyrin molecule, which then generates singlet oxygen necessary to produce photosensitizing effect. This methodology will help to treat nodular and deeper tumours due to higher penetrating capacity of X-rays and gamma rays compared to that of visible light commonly used in PDT.

Fig. 6

Quenching of ADPA photoluminescence (PL) with X-ray irradiation in water (a), ADPA in MTCP solution (b), ADPA in LaF₃:Tb³⁺-MTCP conjugate (c) and ADPA in LaF₃:Tb³⁺-MTCP-folic acid conjugate (d). Reprinted with permission from Ref. [162] ^© 2008 American Institute of Physics.

Fig. 7

Cytotoxicity (left bars for each sample) and phototoxicity (right bars for each sample) of 3×10⁻⁵ M ZnO, 3×10⁻⁵ M MTCP and 3×10⁻⁵ M ZnO-MTCP on NIH-OVCAR-3 cells. Reprinted with permission from Ref. [164] ^© 2008 American Institute of Physics.